This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In mammals, the motor cortex plays a crucial role in controlling limb movements. After losing connections between motor cortex and muscles (as in spinal cord injury or lesions of the corticospinal tract) primates lose their ability to voluntarily activate distal limb muscles, although cortex and muscles may still be functional. Toward testing whether this gap can be bridged with an artificial connection, we have developed an implantable "brain-computer interface" [BCI]. This so-called Neurochip amplifies and detects the activity of a motor cortical neuron, and can convert the recorded action potentials to stimulus pulses delivered to muscles. Monkeys learned to use cortical cell activity to trigger functional electrical stimulation of muscles paralyzed by nerve block, thereby generating appropriate forces to acquire torque targets. These artificial connections could be used independently of whether the cell had been related to movement or not. In contrast to conventional approaches to "brain-machine interfaces" that are based on decoding of movement-related signals in large populations of neurons, this approach uses the activity of relatively few cells connected directly to muscles. To date the demonstration of this paradigm has employed laboratory instrumentation, but implantable Neurochips will provide longer times to incorporate the new circuit into normal behavior. In another application, continuous operation of artificial recurrent connections between cortical sites has produced long-term plasticity in cortical connections, evidenced by changes in the output effects evoked by microstimulation of the connected sites. We have now shown that plasticity can also be induced by a recurrent BCI that delivers stimuli triggered by forearm muscle activity to cortical sites. The recurrent BCI has clinical potential to aid patients paralyzed by ALS or spinal injury to regain some motor control directly from cortical cells and may also strengthen weak connections.